Neurodegenerative diseases caused by denaturation and falling off of nerve cells of the central nervous system are known to accompany injury of a particular site for each disease. Among them are Parkinson's disease and Huntington's disease wherein nerve cells of the basal nucleus, which is a major constituent region of the extrapyramidal tract that controls and regulates the motility function, are injured. The former is caused by denaturation of dopaminergic neuron that projects from the substantia nigra pars compacta to the striatum (non-patent document 1), and the latter is caused by denaturation of GABAergic neuron that projects from the striatum to the globus pallidus and substantia nigra pars reticulata (non-patent document 2). The both are designated as the object of specific disease treatment research program as diseases with high refractory nature and high severity, and further clarification of the cause and the development of a therapeutic drug are expected. Huntington's disease is a dominantly-inherited disease which is developed in a little under 1 in 10,000 Caucasians and up to 1 in several 10,000 people of other races. Particularly the symptoms become serious when a causative gene derived from a father is present. The symptoms thereof include motor symptoms called dystonia such as abnormal involuntary movements and abnormal posture, as well as psychological symptoms such as depression, dementia and the like. While the development of a new drug for Huntington's disease has been tried and plural candidate substances have been recited; however, effectiveness has not been established to date (non-patent document 3).
Of the symptoms of Huntington's disease, L-DOPA preparations have been empirically administered for dystonia (non-patent document 4). Although L-DOPA preparation shows superior effectiveness, it shows a short duration of action, effect variation (wearing off, on-off) and symptoms of dyskinesia and the like due to a long-term use, thus degrading the patients' QOL. Therefore, dopamine agonist providing an effect next to L-DOPA preparation and having a long duration of action has been drawing attention. At present, 6 kinds of dopamine agonists are clinically used in Japan. Particularly, pramipexole is reported to show a treatment effect for myotonia in the Huntington's disease (non-patent document 5), and establishment of the effectiveness is expected.
Under the circumstances, several Huntington's disease-like animal models have been established for the evaluation of and screening for a therapeutic drug for Huntington's disease. The initially reported Huntington's disease-like model mouse is R6/2 mouse introduced with exon1 of Huntington's disease gene that the patients with Huntington's disease have. Although nerve cell death is not observed, symptoms of a decrease in the brain weight, a low muscle amount, an increase in the amount of calorie intake, an increase in the urination frequency, drastic shortening of life span, clasping, tremor and the like have been reported (non-patent document 6). However, since Huntington's disease-like animal models die at the age of 10-12 weeks on average, a long-term study of drug effect is difficult. Moreover, since the symptoms thereof are wide-ranging and go beyond the motor disorder, specific functional analysis is problematically difficult. As a model mouse developed to solve all these problems, which does not induce nerve cell death, a knock-in mouse having a CAG repeat sequence obtained from human Huntington's disease patients has been reported (non-patent documents 7, 8). However, there is an increasing need for a model suitable for the study of a new drug aiming to improve motor symptoms.